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1cjb

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Revision as of 04:18, 10 February 2016

MALARIAL PURINE PHOSPHORIBOSYLTRANSFERASE

Structural highlights

1cjb is a 4 chain structure with sequence from Plafa. The July 2012 RCSB PDB Molecule of the Month feature on Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) by David Goodsell is 10.2210/rcsb_pdb/mom_2012_7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Activity:	Hypoxanthine phosphoribosyltransferase, with EC number 2.4.2.8
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[HGXR_PLAFG] Converts guanine to guanosine monophosphate, and hypoxanthine to inosine monophosphate. Transfers the 5-phosphoribosyl group from 5-phosphoribosylpyrophosphate onto the purine. Works with guanine, hypoxanthine and xanthine. Plays a central role in the generation of purine nucleotides through the purine salvage pathway.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Malaria is a leading cause of worldwide mortality from infectious disease. Plasmodium falciparum proliferation in human erythrocytes requires purine salvage by hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRTase). The enzyme is a target for the development of novel antimalarials. Design and synthesis of transition-state analogue inhibitors permitted cocrystallization with the malarial enzyme and refinement of the complex to 2.0 A resolution. Catalytic site contacts in the malarial enzyme are similar to those of human hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) despite distinct substrate specificity. The crystal structure of malarial HGXPRTase with bound inhibitor, pyrophosphate, and two Mg(2+) ions reveals features unique to the transition-state analogue complex. Substrate-assisted catalysis occurs by ribooxocarbenium stabilization from the O5' lone pair and a pyrophosphate oxygen. A dissociative reaction coordinate path is implicated in which the primary reaction coordinate motion is the ribosyl C1' in motion between relatively immobile purine base and (Mg)(2)-pyrophosphate. Several short hydrogen bonds form in the complex of the enzyme and inhibitor. The proton NMR spectrum of the transition-state analogue complex of malarial HGXPRTase contains two downfield signals at 14.3 and 15.3 ppm. Despite the structural similarity to the human enzyme, the NMR spectra of the complexes reveal differences in hydrogen bonding between the transition-state analogue complexes of the human and malarial HG(X)PRTases. The X-ray crystal structures and NMR spectra reveal chemical and structural features that suggest a strategy for the design of malaria-specific transition-state inhibitors.

The 2.0 A structure of malarial purine phosphoribosyltransferase in complex with a transition-state analogue inhibitor.,Shi W, Li CM, Tyler PC, Furneaux RH, Cahill SM, Girvin ME, Grubmeyer C, Schramm VL, Almo SC Biochemistry. 1999 Aug 3;38(31):9872-80. PMID:10433693^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Shi W, Li CM, Tyler PC, Furneaux RH, Cahill SM, Girvin ME, Grubmeyer C, Schramm VL, Almo SC. The 2.0 A structure of malarial purine phosphoribosyltransferase in complex with a transition-state analogue inhibitor. Biochemistry. 1999 Aug 3;38(31):9872-80. PMID:10433693 doi:10.1021/bi990664p

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1cjb"

@@ Line 2: / Line 2: @@
 <StructureSection load='1cjb' size='340' side='right' caption='[[1cjb]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1cjb]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Plafa Plafa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CJB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1CJB FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1cjb]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Plafa Plafa]. The July 2012 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Hypoxanthine-guanine phosphoribosyltransferase (HGPRT)''  by David Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2012_7 10.2210/rcsb_pdb/mom_2012_7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CJB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1CJB FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IRP:(1S)-1(9-DEAZAHYPOXANTHIN-9YL)1,4-DIDEOXY-1,4-IMINO-D-RIBITOL-5-PHOSPHATE'>IRP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=POP:PYROPHOSPHATE+2-'>POP</scene></td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hypoxanthine_phosphoribosyltransferase Hypoxanthine phosphoribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.8 2.4.2.8] </span></td></tr>
@@ Line 17: / Line 17: @@
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1cjb ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 37: / Line 37: @@
 [[Category: Hypoxanthine phosphoribosyltransferase]]
 [[Category: Plafa]]
+[[Category: RCSB PDB Molecule of the Month]]
 [[Category: Almo, S C]]
 [[Category: Cahill, S M]]

1cjb

From Proteopedia

Revision as of 04:18, 10 February 2016

MALARIAL PURINE PHOSPHORIBOSYLTRANSFERASE

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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